B-Cell Lymphoma ICYMI

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

Key clinical point: Acalabrutinib demonstrates favorable long-term efficacy and safety in patients with relapsed or refractory mantle cell lymphoma (MCL), including those with poor prognostic factors.

Major finding: The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, median duration of response and progression-free survival were 28.6 (95% CI 17.5-39.1) and 22.0 (95% CI 16.6-33.3) months, respectively. No new safety signals were observed.

Study details: The data represent the final results of the phase 2 ACE-LY-004 study of 124 adult patients with MCL, including those with poor prognostic factors, such as blastoid or pleomorphic morphology and Ki-67 index of >30%, who relapsed after or were refractory to ≤ 5 previous therapies and received acalabrutinib twice daily.

Disclosures: This study was funded by AstraZeneca. Some authors declared serving as consultants, advisors, or speakers for and receiving research funds or travel or accommodation expenses from various sources, including AstraZeneca. Two authors declared being employees or equity holders of AstraZeneca.

Source: Le Gouill S et al. Final results and overall survival data from a phase II study of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma, including those with poor prognostic factors. Haematologica. 2023 (Jul 20). doi: 10.3324/haematol.2022.282469

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

Key clinical point: Compared with Bruton tyrosine kinase inhibitors (BTKi) alone, BTKi + anti-CD20 monoclonal antibodies (mAb) demonstrated better efficacy in patients with untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL) without causing safety concerns.

Major finding: The BTKi + anti-CD20 mAb therapy vs BTKi monotherapy group had significantly improved progression-free survival (hazard ratio 0.70; 95% CI 0.51-0.97), complete response rate (relative risk [RR] 2.03; 95% CI 1.01-4.06), and undetectable minimal residual disease rate (RR 6.43; 95% CI 3.54-11.67) and a similar risk for grade ≥3 adverse events (RR 1.08; 95% CI 0.80-1.45).

Study details: Findings are from a meta-analysis of 4 randomized controlled trials including 1056 patients who received a BTKi + anti-CD20 mAb or BTKi monotherapy for untreated, relapsed, or refractory CLL.

Disclosures: This study was supported by grants from the National Science and Technology Council in Taiwan and the industry-academia cooperation program. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of add-on anti-CD20 monoclonal antibody to Bruton tyrosine kinase inhibitor treatment for chronic lymphocytic leukemia: A meta-analysis. Sci Rep. 2023;13:9775 (Jun 16). Doi: 10.1038/s41598-023-36279-x

Key clinical point: Compared with Bruton tyrosine kinase inhibitors (BTKi) alone, BTKi + anti-CD20 monoclonal antibodies (mAb) demonstrated better efficacy in patients with untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL) without causing safety concerns.

Major finding: The BTKi + anti-CD20 mAb therapy vs BTKi monotherapy group had significantly improved progression-free survival (hazard ratio 0.70; 95% CI 0.51-0.97), complete response rate (relative risk [RR] 2.03; 95% CI 1.01-4.06), and undetectable minimal residual disease rate (RR 6.43; 95% CI 3.54-11.67) and a similar risk for grade ≥3 adverse events (RR 1.08; 95% CI 0.80-1.45).

Study details: Findings are from a meta-analysis of 4 randomized controlled trials including 1056 patients who received a BTKi + anti-CD20 mAb or BTKi monotherapy for untreated, relapsed, or refractory CLL.

Disclosures: This study was supported by grants from the National Science and Technology Council in Taiwan and the industry-academia cooperation program. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of add-on anti-CD20 monoclonal antibody to Bruton tyrosine kinase inhibitor treatment for chronic lymphocytic leukemia: A meta-analysis. Sci Rep. 2023;13:9775 (Jun 16). Doi: 10.1038/s41598-023-36279-x

Key clinical point: Compared with Bruton tyrosine kinase inhibitors (BTKi) alone, BTKi + anti-CD20 monoclonal antibodies (mAb) demonstrated better efficacy in patients with untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL) without causing safety concerns.

Major finding: The BTKi + anti-CD20 mAb therapy vs BTKi monotherapy group had significantly improved progression-free survival (hazard ratio 0.70; 95% CI 0.51-0.97), complete response rate (relative risk [RR] 2.03; 95% CI 1.01-4.06), and undetectable minimal residual disease rate (RR 6.43; 95% CI 3.54-11.67) and a similar risk for grade ≥3 adverse events (RR 1.08; 95% CI 0.80-1.45).

Study details: Findings are from a meta-analysis of 4 randomized controlled trials including 1056 patients who received a BTKi + anti-CD20 mAb or BTKi monotherapy for untreated, relapsed, or refractory CLL.

Disclosures: This study was supported by grants from the National Science and Technology Council in Taiwan and the industry-academia cooperation program. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of add-on anti-CD20 monoclonal antibody to Bruton tyrosine kinase inhibitor treatment for chronic lymphocytic leukemia: A meta-analysis. Sci Rep. 2023;13:9775 (Jun 16). Doi: 10.1038/s41598-023-36279-x

Key clinical point: The presence of one or more lymph nodes >56.5 mm before starting venetoclax is an independent risk factor for early progression during venetoclax therapy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: After a median follow up of 14.3 months, the median progression-free survival (PFS) was not reached and the estimated 3‐year PFS rate was 54%. Multivariable analysis revealed a >56.5 mm diameter of at least one lymph node before therapy initiation to be a significant predictive factor for progression (adjusted hazard ratio 1.01; P =.005).

Study details: Findings are from a multicenter retrospective study including 128 patients with relapsed or refractory CLL treated with ibrutinib, idelalisib, or both who switched to venetoclax due to progression or adverse events, of which 28 patients experienced progressive disease.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Autore F et al. Lymphadenopathy as a predictor of progression during venetoclax treatment in chronic lymphocytic leukemia. A campus chronic lymphocytic leukemia study. Hematol Oncol. 2023 (Jul 1). Doi: 10.1002/hon.3199

Key clinical point: The presence of one or more lymph nodes >56.5 mm before starting venetoclax is an independent risk factor for early progression during venetoclax therapy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: After a median follow up of 14.3 months, the median progression-free survival (PFS) was not reached and the estimated 3‐year PFS rate was 54%. Multivariable analysis revealed a >56.5 mm diameter of at least one lymph node before therapy initiation to be a significant predictive factor for progression (adjusted hazard ratio 1.01; P =.005).

Study details: Findings are from a multicenter retrospective study including 128 patients with relapsed or refractory CLL treated with ibrutinib, idelalisib, or both who switched to venetoclax due to progression or adverse events, of which 28 patients experienced progressive disease.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Autore F et al. Lymphadenopathy as a predictor of progression during venetoclax treatment in chronic lymphocytic leukemia. A campus chronic lymphocytic leukemia study. Hematol Oncol. 2023 (Jul 1). Doi: 10.1002/hon.3199

Key clinical point: The presence of one or more lymph nodes >56.5 mm before starting venetoclax is an independent risk factor for early progression during venetoclax therapy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: After a median follow up of 14.3 months, the median progression-free survival (PFS) was not reached and the estimated 3‐year PFS rate was 54%. Multivariable analysis revealed a >56.5 mm diameter of at least one lymph node before therapy initiation to be a significant predictive factor for progression (adjusted hazard ratio 1.01; P =.005).

Study details: Findings are from a multicenter retrospective study including 128 patients with relapsed or refractory CLL treated with ibrutinib, idelalisib, or both who switched to venetoclax due to progression or adverse events, of which 28 patients experienced progressive disease.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Autore F et al. Lymphadenopathy as a predictor of progression during venetoclax treatment in chronic lymphocytic leukemia. A campus chronic lymphocytic leukemia study. Hematol Oncol. 2023 (Jul 1). Doi: 10.1002/hon.3199

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278